butylation

Butylation is the chemical process of introducing a butyl group (C4H9) into a molecule. The butyl group can be n-, sec-, iso-, or tert-, and the term covers reactions that form C–C, C–O, or C–N bonds bearing a butyl substituent. In organic synthesis, butylation is most commonly discussed in the context of alkylation, particularly of aromatic rings or other electrophilic centers.

A frequently used method is Friedel–Crafts alkylation, where a butyl halide reacts with an arene in the presence of a Lewis acid such as aluminum chloride. tert-Butyl reagents are especially common because tert-butyl cations form readily and tend to minimize rearrangements, though primary and secondary butyl halides can undergo carbocation rearrangements or side reactions, reducing selectivity.

Other routes to butylation include SN2 alkylation (as in Williamson ether synthesis) to form butyl ethers from alcohols and butyl halides, and various organometallic approaches where Grignard or organolithium reagents add to carbonyl compounds to install a butyl group, followed by workup to give higher alcohols.

Applications and considerations: butylation is used to adjust the lipophilicity, steric profile, and reactivity of molecules in pharmaceuticals, fragrances, and polymers. The tert-butyl group is widely used as a protecting group in multi-step syntheses, while butyl esters and other butylated derivatives serve as intermediates and additives in industrial chemistry. Safety concerns include handling of alkyl halides and strong Lewis acids, which can be hazardous and reactive.